HYPOGLYCEMIC AGENTS

1
HYPOGLYCEMICAGENTS

• Rama B. Rao, M.D.
• Bellevue Hospital Center/NYUMC
• New York, N.Y.

2
Glycemic Control Agents

• Insulin
• Sulfonylureas
• Meglitinides Repaglinide
• Biguanides Metformin
• Thiazolidinediones Pioglitazone
• ? Glucosidase inhibitors

3
MUSCLE CELL
I
Glycogen
Storage
P
I
Glucose
Pyruvate
Oxidative
ATP
Krebs
Phosphorylation
Cycle
4
MUSCLE CELLS
Glycogen
P
I
EPINEPHRINE
GLUCAGON
Glucose
Pyruvate
Oxidative
ATP
Krebs
Phosphorylation
5
MUSCLE CELLS
FFA
P
I
KETONES
Glucose
Pyruvate
ATP
Oxidative
Krebs
Phosphorylation
6
BRAIN
Glycogen
KETONES
Pyruvate
P
Glucose
Oxidative Phosphorylation
Krebs
ATP
7
HYPOGLYCEMIA

• Hunger/Anxiety
• Focal neurological deficits
• Confusion
• Seizures
• Coma
• Hypothermia

8
BRAIN Anterior Pituitary
ATP
P
Glucose
GH EXCITATORY NT
Adrenal medulla
Catecholamines
9
Other Manifestations

• Tachycardia
• Tremor
• Diaphoresis

10
ALPHA CELL OF PANCREAS
Decreased
Glucose
GLUCAGON
Catecholamines, Amino acids
11
MUSCLE CELLS
Glycogen
P
I
EPINEPHRINE
GLUCAGON
Glucose
Pyruvate
Oxidative
ATP
Krebs
Phosphorylation
12
LIVER CELL
I
Glycogen
Storage
EPINEPHRINE
P
GLUCAGON
Glucose
Pyruvate
ATP
Oxidative
Krebs
Phosphorylation
Cycle
13
PANCREAS BETA ISLET CELL
Insulin


Ca2
MEMBRANE DEPOLARIZATION
14
PANCREAS BETA ISLET CELL
Insulin
K
ATP

Ca2
Sulfonylurea, Meglitinides
Repaglinide
15
SULFONYLUREAS

• Risk of hypoglycemia
• Fasting
• Elderly variable data
• Chronic renal failure

16
SULFONYLUREA INDUCED HYPOGLYEMIA

• Administration of glucose for acute correction
• Decontamination
• Nutrition, IV access
• Admission

17
SULFONYLUREAS

• Monitor potassium, phosphate
• Urinary alkalinization for chlorpropamide
• Octreotide for refractory hypoglycemia
• Observation for at least 12 hours after last
  dose octreotide

18
Octreotide Dosing

• Adults 50 ?g subcutaneously every 6 hours
• Children 4-5 ?g/kg/day subcutaneously divided
  every 6 hours, with maximum not exceeding the
  adult dose

19
PANCREAS BETA ISLET CELL
Insulin
K
ATP
- - - - -
- - -
Ca2
DIAZOXIDE
20
PANCREAS BETA ISLET CELL
Insulin
G
Ca2
OCTREOTIDE
21
SUFONYLUREAS Other Effects

• Inhibition of aldehyde dehydrogenase
• SIADH

22
INSULIN

• Oral exposure is benign
• Parenteral Exposures
• Unpredictable in overdose
• May be dependent upon quantity injection
• Formulation
• Treatment nutrition, supplemental glucose
  infusion

23
HYPOGLYCEMICS MANAGEMENT

• Identify and treat hypoglycemia
• Admission especially if brought to coma or
  seizure
• Nutrition
• Consider enteral infusion of feeds via NG Tube
• Monitor electrolytes

24
GLUCOSE ADMINISTRATION

• Adults
• D50W 1 gram/kg
• Children
• D25W 0.5-1 gram/kg
• D10 W 0.5-1 gram/kg in neonates
• Infusion of D10 W at a total of 1 gram/kg/hr
• Monitor potassium

25
METFORMIN

• Rarely causes true hypoglycemia
• Adverse reaction
• Lactic acidosis only in patients with renal
  insufficiency or shock states.
• Treatment of lactic acidosis hemodialysis
• 
  
• Caveat Co-ingested substances

26
MUSCLE CELL
Glycogen
P
I
Glucose
Pyruvate
METFORMIN
Oxidative
ATP
Phosphorylation
Krebs
27
LIVER CELL
Glycogen
P
Pyruvate
Oxidative
ATP
Phosphorylation
METFORMIN
28
OTHER AGENTS AFFECTING CARBOHYDRATE METABOLISM

• Ethanol
• Beta adrenergic antagonists
• Unripened ackee fruit
• Valproic acid
• Salicylates
• Pentamidine

• Quinidine
• Disopyramide

29
LIVER CELL
Glycogen
Pyruvate
Glucose
Oxidative
Phosphorylation
NADHH
Acetate
ATP
ETHANOL
NAD
Lactate
30
ALPHA CELL OF PANCREAS
Decreased
Glucose
GLUCAGON
BETA ADRENERGIC
ANTAGONISTS
Catecholamines, Amino acids
31
LIVER CELL
Glycogen
P
Pyruvate
Oxidative
ATP
Phosphorylation
ACKEE
32
LIVER
FFA
ACKEE
VALPROIC ACID
P
I
KETONES
Glucose
Pyruvate
ATP
Oxidative
Krebs
Phosphorylation
33
LIVER
P
I
Glucose
Pyruvate
Alanine
ATP
Oxidative
Krebs
Phosphorylation
SALICYLATES
34
PANCREAS BETA ISLET CELL
Insulin
PENTAMIDINE
ALLOXAN
STREPTOZOCIN


Ca2
Membrane depolarization
35
BRAIN
Pyruvate
P
THIAMINE
Acetyl Co A
Oxidative Phosphorylation
GLUCOSE
Krebs
ATP
36
MUSCLE CELL
I
Glycogen
Storage
P
I
Glucose
Pyruvate
Oxidative
ATP
Krebs
Phosphorylation
Cycle
37
MUSCLE CELLS
Glycogen
P
I
EPINEPHRINE
GLUCAGON
Glucose
Pyruvate
Oxidative
ATP
Krebs
Phosphorylation
38
MUSCLE CELLS
FFA
P
I
KETONES
Glucose
Pyruvate
ATP
Oxidative
Krebs
Phosphorylation
39
BRAIN
Glycogen
KETONES
Pyruvate
P
Glucose
Oxidative Phosphorylation
Krebs
ATP
40
LIVER CELL
I
Glycogen
Storage
EPINEPHRINE
P
GLUCAGON
Glucose
Pyruvate
ATP
Oxidative
Krebs
Phosphorylation
Cycle